ProMACE/CytaBOM方案治疗难治性或复发性非霍奇金淋巴瘤的疗效观察

目的：探讨ProMACE/CytaBOM方案治疗难治性和(或)复发性非霍奇金淋巴瘤(NHL)的疗效。方法：采用ProMACE／CytaBOM方案治疗18例难治性和(或)复发性NHL患者，其中难治性NHL患者8例，复发性NHL患者10例。结果：5例难治性和(或)复发性NHL患者达到完全缓解(CR率为27．8％)，4例达部分缓解(PR率为22．2％)，总有效率为50．0％；目前12例仍生存，其中生存最长者26个月(2例)，仍处于CR期。毒副作用主要为消化道症状、轻度肝功能异常以及骨髓抑制。结论：ProMACE／CytaBOM方案对部分难治性和(或)复发性NHL患者仍有效，毒副作用较轻，可用于治疗对其他化疗方案无效的难治性和(或)复发性NHL。     

New indicators for delay in initiation of antiretroviral treatment: estimates for Cameroon

Objective

To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon.

Methods

We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d’Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010.

Findings

In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/μl (interquartile range, IQR: 66 to 210) in 2007–2009 to 163 cells/μl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2).

Conclusion

The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful.     

Non-bacterial thrombotic (marantic) endocarditis associated with giant-cell arteritis

A patient with giant-cell arteritis and non-bacterial thrombotic (marantic) endocarditis of the mitral valve is described. To our knowledge, this is the first case reported. The importance of revising the diagnosis of infective endocarditis when no pathogen can be demonstrated is emphasized.     

Effects of insulin resistance and insulin secretion on the efficacy of interventions to retard development of type 2 diabetes mellitus: the DA Qing IGT and Diabetes Study

OBJECTIVE: To investigate the effects of insulin resistance (IR) and insulin secretion (IS) on the development of diabetes mellitus in individuals with impaired glucose tolerance (IGT) who underwent lifestyle interventions. METHODS: 284 out of 577 individuals with IGT identified by population-based screening in Da Qing, China, who were randomized to undergo diet change and/or increased physical activity had baseline fasting and 2 h post-load insulin determinations. They were followed for 6 years for the development of diabetes. IR and IS were assessed using calculated indices based on fasting plasma insulin and glucose. The interactions of IR, IS, obesity and plasma glucose and the effects of the lifestyle interventions were evaluated using Cox Proportional Hazards analysis. RESULTS: Both IR and IS were significantly associated with the development of diabetes. Lifestyle interventions were more effective in those with lower IT and higher IS at baseline. Diet plus exercise interventions resulted in significantly lower incidence of diabetes, even after controlling for IR, IS, BMI and 2hrPG. CONCLUSION: Both IR and beta-cell function were predictors of diabetes in Chinese with IGT. Lifestyle intervention reduced the incidence of DM and these interventions were more effective in those with less IR.     

Cine magnetic resonance imaging for evaluation of anatomy and flow relations in infants and children with coarctation of the aorta

Sixteen cine magnetic resonance imaging (MRI) studies were performed in 14 patients aged 1 week to 17 years (mean age, 46 months), who had coarctation of the aorta confirmed at angiography or surgery. Conventional echocardiographic-gated MRI was first performed in axial and rotated sagittal views and was used to identify the slice locations for cine MRI. Cine MRI was performed by gradient-recalled acquisition in steady state with a 30 degree flip angle, 12-msec echo time, 22-msec pulse repetition time, and a 128 x 256 acquisition matrix. Coarctation anatomy was extremely well defined in all but one patient who had vascular clips at the coarctation repair site. The smallest descending aortic flow diameter on cine MRI showed excellent agreement with angiography (r = 0.90). Lucent jets of high-velocity flow through the site of coarctation were imaged in eight patients, and jet length correlated well with the angiographic severity of coarctation (r = -0.81). Two patients were restudied after surgery, and they exhibited excellent repair and normal flow patterns. Cine MRI provides high-resolution imaging of coarctation anatomy with a dynamic spatial and temporal visualization of flow and with excellent detail of vascular anatomy and flow both proximal and distal to the coarctation.     

The influence of co-morbidity on health-related quality of life in asthma and COPD patients

This study examines the association between somatic co-morbidity and both general and disease-specific health-related quality of life (HRQoL) in patients with asthma and chronic obstructive pulmonary disease (COPD). A cross-sectional analysis was done among 161 COPD patients and 395 asthma patients, aged 40-75 years, recruited from general practice. In the total study population, 47% had no, 32% had one, and 21% had two or more somatic co-morbid conditions, with no significant differences between asthma and COPD patients. Co-morbidity appeared to be associated with poor disease-specific HRQoL in asthma [odds ratio (OR) = 2.08 (1.37-3.18)] and with poor general HRQoL in asthma [OR = 2.96 (1.93-4.53)] and COPD [1.81 (0.91-3.60)] patients. Poorest HRQoL was found in patients with more than one co-morbid condition. Cardiac disease and hypertension were associated with poor disease-specific HRQoL in asthma. Of all co-morbid conditions, musculoskeletal disorders were most strongly associated with poor general HRQoL. Cardiac disease was found to be associated with general and disease-specific HRQoL in asthma but not in COPD. In studies on patients with asthma or COPD aged 40-75 years, co-morbidity should be treated as a determinant of HRQoL.     

The Aptima HPV Assay Fulfills the Cross-Sectional Clinical and Reproducibility Criteria of International Guidelines for Human Papillomavirus Test Requirements for Cervical Screening

The Aptima HPV assay (Hologic Gen-Probe, San Diego, CA) is an FDA-approved assay for detecting human papillomavirus (HPV) E6/E7 mRNA from 14 high-risk HPV types. This study evaluated the clinical performance of the Aptima HPV assay for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+), relative to the high-risk HPV GP5+/GP6+ PCR, in a cross-sectional clinical equivalence analysis using the noninferiority score test with cervical samples from population-based screening, i.e., 69 cervical scraping samples from women with CIN2+ and 843 from women without evidence of CIN2+. In addition, intralaboratory reproducibility over time and interlaboratory agreement of the Aptima HPV assay results were assessed with another set of 548 cervical samples. The Aptima HPV assay showed a clinical sensitivity for CIN2+ of 94.2% (95% confidence interval [CI], 85.5 to 97.8%) and a clinical specificity for CIN2+ of 94.5% (95% CI, 92.8 to 95.9%); by comparison, these figures were 97.1% (95% CI, 89.1 to 99.3%) (67/69 samples) and 93.6% (95% CI, 91.7 to 95.0%) (785/839 samples), respectively, for GP5+/GP6+ PCR. The clinical sensitivity and specificity of the Aptima HPV assay were noninferior to those of GP5+/GP6+ PCR (P = 0.039 and 0.00016, respectively). In addition, high reproducibility of the Aptima HPV assay, as reflected by the intralaboratory reproducibility over time of 96.0% (95% CI, 94.4 to 97.3%) (526/548 samples; kappa = 0.89) and interlaboratory agreement of 96.7% (95% CI, 95.4 to 98.1%) (531/548 samples; kappa = 0.91), was found. Altogether, these data show that the Aptima HPV assay meets the cross-sectional clinical and reproducibility criteria of the international guidelines for HPV test requirements for cervical screening. Longitudinal data are needed to ensure that the long-term negative predictive value of this mRNA assay is similar to those of validated HPV DNA tests.     

Evidence for a Direct Effect of the NAD+ Precursor Acipimox on Muscle Mitochondrial Function in Humans

Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD⁺) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD⁺ precursor, would directly affect mitochondrial function independent of reductions in nonesterified fatty acid (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 ± 1.1 years, BMI 33.4 ± 0.8 kg/m²) received either placebo or acipimox 250 mg three times daily dosage for 2 weeks. Acipimox treatment increased plasma NEFA levels (759 ± 44 vs. 1,135 ± 97 μmol/L for placebo vs. acipimox, P < 0.01) owing to a previously described rebound effect. As a result, skeletal muscle lipid content increased and insulin sensitivity decreased. Despite the elevated plasma NEFA levels, ex vivo mitochondrial respiration in skeletal muscle increased. Subsequently, we showed that acipimox treatment resulted in a robust elevation in expression of nuclear-encoded mitochondrial gene sets and a mitonuclear protein imbalance, which may indicate activation of the mitochondrial unfolded protein response. Further studies in C2C12 myotubes confirmed a direct effect of acipimox on NAD⁺ levels, mitonuclear protein imbalance, and mitochondrial oxidative capacity. To the best of our knowledge, this study is the first to demonstrate that NAD⁺ boosters can also directly affect skeletal muscle mitochondrial function in humans.     

Interleukin-11 stimulates multilineage progenitors, but not stem cells, in murine and human long-term marrow cultures

Interleukin-11 (IL-11) is a bone marrow microenvironment-derived growth factor with pleiotropic effects on a variety of hematopoietic cells. To more accurately assess the effects of IL-11 on stem and progenitor compartments within the hematopoietic microenvironment (HM), we added recombinant human (rh) IL-11 to human and murine long-term bone marrow cultures (LTMC) and analyzed primitive (high proliferative potential- colony forming cells [HPP-CFC], long-term culture-initiating cells [LTC- IC], and long-term reconstituting stem cells) and progenitor (day 12 colony forming unit-spleen [CFU-S12], colony forming unit-megakaryocyte [CFU-Mk] and colony forming unit-granulocyte/macrophage [CFU-GM]) compartments throughout the duration of the cultures. rhIL-11 (100 ng/mL) added twice weekly resulted in significantly increased nonadherent (NA) cellularity, CFU-GM, and CFU-Mk production in human LTMC. Addition of rhIL-11 to murine LTMC was associated with a 5- to 40- fold increase in CFU-GM and a four- to 20-fold increase in day 12 CFU-S in NA cells. However, IL-11 had no significant effect on total HPP-CFC concentration and decreased the size of the more primitive stem/progenitor compartment as evidenced by both decreased LTC-IC frequency in human LTMC and decreased frequency of long-term reconstituting stem cells in murine LTMC. These data suggest that IL-11 may increase commitment of stem cells into a multipotential progenitor compartment.     

Acquired immune hemolytic anemia associated with IgA erythrocyte coating: investigation of hemolytic mechanisms

We have investigated the hemolytic mechanisms in a patient with acquired immune hemolytic anemia whose red cells appeared to be coated with IgA alone. The clinical course was similar to that of patients with hemolytic anemia mediated by warm-reacting IgG antibody. Splenic sequestration of red cells was demonstrated, and marked reduction of hemolysis occurred after corticosteroid therapy. Antibody was eluted from the patient's red cells and used to sensitize normal red cells in vitro. These sensitized red cells were not lysed by fresh autologous serum, nor did they fix detectable amounts of C3. However, red cells sensitized by eluted antibody were lysed by normal human peripheral blood monocytes in a system designed to demonstrate antibody-dependent cell-mediated cytotoxicity. Monocyte-mediated hemolysis of sensitized red cells was inhibited by the addition of low concentrations of normal serum IgA to the system, but not by IgG. The ability of the eluate to induce monocyte-mediated hemolysis was abolished by its adsorption on Sepharose-bound anti-IgA, but not by preincubation with Sepharose-bound anti-IgG. In addition, normal human monocytes were demonstrated to ingest eluate-sensitized red cells. These data demonstrate an in vitro interaction of IgA-sensitized red cells with leukocytes and suggest a possible mechanism for the patient's hemolysis.